Even after being put through withdrawal and then given access to heroin again, the vaccinated rats don’t seek it out.

“The effects of the heroin vaccine are more dramatic than any we’ve ever seen and have been tested more rigorously in an animal model than we’ve every seen,” said George Koob, the study’s senior author.

The study, conducted entirely by Scripps scientists, was published online Monday in the Proceedings of the National Academy of Sciences. The first author was Joel E. Schlosburg.

Senior study author Kim Janda says the vaccine causes the body to produce antibodies against heroin and its psychoactive products. These antibodies circulate in the bloodstream, and neutralize any of these substances they encounter before they reach the brain.

“It’s like the old ’80s game Pac-Man,” Janda said. “They immediately seek out the target and sequester it.”

The vaccine isn’t intended to provide a one-step solution for heroin addicts, Koob said. It’s meant to help addicts who want to get off the drug, by eliminating the damaging effect of a relapse.

Money is the main obstacle to beginning human testing, say the researchers, who are looking for a drug company or perhaps a philanthropist to fund the clinical trials.

The trial would be relatively inexpensive, Koob said.

“My guess is it would be less than the millions of dollars that need to be done for, say, an antidepressant,” Koob said.

George Koob chairs the committee On The Neurobiology Of Addictive Disorders at The Scripps Research Institute in La Jolla. — Bradley J. Fikes/U-T San Diego

Kim Janda explains heroin vaccine genesis

Kim Janda explains how he arrived at the idea of using catalytic antibodies in an anti-addiction vaccine.

Bob Patton, a research fellow at the National Addiction Center at King’s College in London, said the study is promising, but more research is needed to determine how effective it can be upon the “more sophisticated immune and reward systems” of humans.

“It is well understood that addiction is more than a simple physiological condition, and that environmental and social factors play an important role in its onset and maintenance,” Patton said by email. “For this reason, it is encouraging that the authors view their vaccine as an adjunct rather than an alternative for existing therapies.”

Worldwide, an estimated 12 million to 14 million people used heroin as of 2009, according to the United Nations Office on Drugs and Crime. An estimated 281,000 Americans used heroin as of 2011, according to the federal Substance Abuse and Mental Health Services Administration.

Blocking the voluntary resumption of addictive behavior is extraordinarily difficult, said Koob, who chairs the Committee on the Neurobiology of Addictive Disorders at Scripps. Demonstrating that effect in rats gave “definitive” evidence that the vaccine has potential for people.

“That’s never been done before,” Koob said. “No one has ever addicted a rat to nicotine or cocaine and then shown they could stop them from re-addicting themselves.”

Such anti-addiction vaccines are safe, and don’t block the effect of painkillers Koob said.

“One of the fears is, it’s going to bind to my endorphins — not,” Koob said. “It’s going to bind to my opiate receptors — not. It’s going to do something to my liver — not. They sit in the bloodstream like a sponge, they grab these molecules when they show up, and activate clearance or destruction of the molecules.”

Koob said one of these metabolites, 6-acetylmorphine, appears to be the most active ingredient in the heroin high, because blocking that molecule stopped the addicted rats from engaging in “reinforcing” behavior.

“We knew that it was formed, we knew that it was active, but we didn’t know how active,” Koob said. “It seems to be even more important than morphine itself.”

Janda said the vaccine’s length of effectiveness in humans remains to be determined; it has been shown to work for a few months in rats.

A key breakthrough was realizing that it wasn’t necessary or even desirable to combat the effect of heroin with another drug, Janda said.

“It occurred to me, I’m developing a drug to treat a drug addiction,” Janda said. “Isn’t that an oxymoron?”

George Koob discusses funding for heroin vaccine

Janda turned to a class of antibodies he had been researching, called catalytic antibodies. Antibodies are made by the body’s immune system to fight invading pathogens. The catalytic antibodies trigger chemical reactions, in this case, reactions that bind heroin and its metabolic derivatives. These reactions take place in the blood, before the psychoactive substances have a chance to reach the brain.

The rats were vaccinated by injecting them with fragments of heroin and morphine molecules, along with a substance to stimulate the immune system. They were given three doses over a 28-day period.

Heroin is tricky for a vaccine because it’s a moving target. Once the molecule enters the bloodstream, it is quickly metabolized into smaller molecules, which have their own psychoactive effects. So the vaccine produces a series of these catalytic antibodies. As each of the metabolites form, the antibodies mop them up. Janda calls this a “dynamic vaccine.”

Koob said one of these metabolites, 6-acetylmorphine, appears to be the most active ingredient in the heroin high, because blocking that molecule stopped the addicted rats from engaging in “reinforcing” behavior.

“We knew that it was formed, we knew that it was active, but we didn’t know how active,” Koob said. “It seems to be even more important than morphine itself.”

Janda said a key breakthrough was realizing that it wasn't necessary or even desirable to combat the effects of heroin with another drug.

"It occurred to me, I'm developing a drug to treat a drug addiction," Janda said. "Isn't that an oxymoron? So I thought, we've been developing these catalytic antibodies. Why not just use antibodies as a means to sequester the drug, and keep it from crossing the blood-brain barrier."

Antibodies and enzymes are both molecules of protein, Janda said, and it proved possible to "teach" the immune system to make antibodies that produced the catalytic effect of enzymes.

Heroin is tricky for a vaccine because it's a moving target. Once the molecule enters the bloodstream, it is quickly metabolized into smaller molecules, which have their own psychoactive effects. So the vaccine produces a series of catalytic antibodies. As each of the metabolites form, the antibodies mop them up. Janda calls this a "dynamic vaccine."

The article is titled, “Dynamic vaccine blocks relapse to compulsive intake of heroin.”